We propose to investigate mainly the mechanisms accountable for hyperserotonemia found in a proportion of autistic and/or severely retarded children as well as in other mentally disturbed child and adult populations as a step toward understanding the clinical significance, if any, of the phenomenon. We will investigate (1) peripheral blood measures of tryptophan metabolism as well as (2) possible platelet abnormalities in hyperserotonemic and normal blood serotonin individuals. We also will determine concomitantly blood and urinary tryptophan metabolites steady-state and following a tryptophan load. Platelet parameters to be investigated include platelet number, MAO activity, uptake, binding and efflux which might cause increased blood levels of serotonin. Because of platelet heterogeneity, we will investigate in a selected group of hyperserotonemic and normal blood serotonin individuals the various platelet parameters in (1) total platelet populations and (2) platelet fractions separated according to density. Pursuing leads from our previous studies, we continue to investigate the frequency and stability with which hyperserotonemia occurs in normals and different disturbed populations; pursue our finding of two types of hyperserotonemia (type A and type B) and attempt to define those mechanisms and clinical correlates characterizing these two types. Finally we intend to expand upon our recent finding of MAO differences, and serotonin and trypotophan differences in (1) chronic paranoid and nonparanoid schizophrenic patients and in (2) patients with Huntington's chorea and their offspring at risk for the disorder. These investigations should yield important information concerning those peripheral, and perphaps central events controlling tryptophan metabolism; e.g. among other tentative hypotheses, a CNS "demand" on serotonergic neural systems, may influence measures of peripheral metabolism.